This prospective high-risk family study, the Michigan Longitudinal Study (MLS) began 27 years ago to characterize the development of risk for alcohol use disorder (AUD) among children (2nd generation or G2s) beginning prior to school entry, with the aims to detect whether risk markers of later disorder could be identified very early, to characterize the evolution of identified risk factors over the course of childhood and early adulthood, and to identify mediators and moderators of risk development that could guide prevention or early intervention programming. Aims for the parents (G1s) were to identify factors that predict relapse, remission, and social adaptation. The project is the earliest beginning (age 3) high risk for AUD study currently active, and involves one of the longest spans of prospective assessment of alcohol/other drug use. Its data matrix involves repeated measurement of a variable network of behavioral, cognitive, and psychological functioning, social environment, substance use/abuse, and psychiatric symptoms. It is also interdigitated with 5 other projects which utilize the MLS as their recruitment, data management, and conceptual core, and share all data. This renewal application proposes continued characterization of G2s as the scientifically most unique segment of the study, limiting G1 assessments to measures critical to characterizing the socialization environment of G2s. G2s have been assessed since preschool and drinking/other drug use is assessed from time of onset. Continued collection of these data will allow evaluation of the prospective effects of precursive risk, in interaction with early substance use, upon later behavior. We intend to fully characterize two critical issues in G2s: 1) Identification of the developmental risk pathways that lead to an AUD outcome without psychiatric comorbidity as contrasted with one involving a comorbid externalizing or internalizing diagnosis; (Aim 1); and 2) Identification of the factors that predict a resilient (non-alcohol abusing) outcome in emerging adulthood, despite precursive exposure to adversity (Aim 2). Furthermore, we intend to take advantage of the comprehensive multi-domain matrix of data available from the core study and its offshoot partner-projects to build cross-level, developmental models of mechanistic structure for critical risk and resilience phenotypes for problem alcohol use and AUD across levels of genes, neural networks, social environment, and development (Aim 3). In order to fully capitalize on the maturity of the study, we will also use th extensive multi-wave database to characterize a critical issue in the G1s: evaluating the long term effects of alcohol consumption burden upon cognitive function in middle to later adulthood (Aim 4). With more than a generation of real time information the project will be able to prospectively evaluate these effects over the course of 27 years. Finally, we intend to provide the now very long-term longitudinal database as a resource for the field. Thus, our final aim is to establish a project development program involving meetings adjunctive to RSA and CPDD for investigators to share data and issues, with the goal of developing a collaborative network (Aim 5).